Abstract: Renal disease in HIV-infected patients has evolved over the 3 decades since the outset of the infection. Whereas HIV-associated nephropathy (HIVAN) manifesting collapsing glomerulopathy, tubular microcysts and endothelial tubuloreticular inclusions predominated early in the epidemic, the incidence of HIVAN has declined following the introduction of anti- retroviral therapy. Despite this trend, the incidence of ESRD has remained unchanged, reflecting the development of other histopathology. This proposal will explore the long-term consequences of HIV infection in the kidney beyond HIVAN. The role of Core B will be to provide technical and interpretative support in light microscopy, immunohistochemistry, immunofluorescence and electron microscopy in mouse and human kidney tissues for all projects. For Specific Aim 1, archived kidney biopsy tissue from HIV positive patients will be selected based on histopathologic diagnosis for investigation of inflammatory pathways identified in the in vitro models using immunohistochemistry and immunofluorescence. In Specific Aim 2, renal pathology in Tg26 mice with different intestinal microbiome will be evaluated and immunostaining performed to quantify immune cell infiltrates. For Specific Aim 3, the hypothesis that chronic HIV infection promotes comorbid disease though enhanced pro- inflammatory response via SIRT-1-regulated NF-kB and STAT3 acetylation and mitochondrial injury will be investigated in murine kidneys and validated in human kidney tissues. Core B will collaborate with the Clinical Core to identify appropriate kidney biopsy samples from the Core C repository or from anonymized archived samples in the Columbia biopsy database as needed.